I will incubate isolated rat hepatocytes under various conditions in order to study the mechanisms regulating 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase activity and cholesterol biosynthesis. I will purify HMG-CoA reductase, prepare antibodies to the homogenous protein and study the turn-over (i.e., synthesis and catabolism) of the enzyme in isolated haptocytes and in the intact animal . BIBLIOGRAPHIC REFERENCES: Control of 3-hydroxy-3-methylglutaryl coenzyme A reductase by endogenously synthesized sterols in vitro and in vivo. PA Edwards, G. Popjak, AM Fogelman and J. Edmond. J. Biol. Chem. in press 1977. Mechanism of Induction of 3-hydroxy-3-methylglutaryl CoA reductase in human leukocytes. AM Fogelman, J. Seager, PA Edwards and G. Popjak. J. Biol Chem. in press 1977.